Spirituality and its role in end-of-life care has emerged as a central issue in palliative care. There have been several recent studies of terminally ill cancer patients, both by our research group and others, demonstrating the central role of spiritual well being, and sense of meaning in particular, in buffering against depression, hopelessness, and desire for hastened death. We have developed, manualized, and pilot-tested just such a novel intervention we call Meaning-Centered Psychotherapy (MCP). MCP, pilot-tested in both an 8-week group format and a 7-session individual format, is based on the principles of Viktor Frankl's work, and is designed to help patients with advanced cancer sustain or enhance a sense of meaning as they approach the end-of-life. Preliminary findings from our pilot randomized controlled trials demonstrate both the group and Individual formats of MCP significantly reduce psychological distress (e.g., depression, hopelessness, anxiety, and desire for hastened death), and significantly increase spiritual well-being and a sense of meaning and purpose in life in advanced cancer patients. However, the individual format of MCP has distinct advantages over the group format, particularly in a palliative care setting, in terms of practicality, flexibility of scheduling, significantly lower attrition and higher rates of delivery of the full dose of treatment. The overall aim of this project is to conduct a randomized controlled trial of the efficacy of an innovative individual psychotherapy intervention for advanced cancer patients. Specifically, we will compare Individual Meaning-Centered Psychotherapy (IMCP) to both a standardized Individual Supportive Psychotherapy (ISP) as well as enhanced usual care (EUC) in order to examine the efficacy of IMCP in enhancing spiritual well-being and quality of life and in reducing psychological distress and end-of-life despair (e.g., hopelessness, desire for hastened death). Specifically, we will compare Individual Meaning-Centered Psychotherapy (IMCP) to both a standardized Individual Supportive Psychotherapy (ISP) as well as enhanced usual care (EUC) in order to examine the efficacy of IMCP in enhancing spiritual well-being and quality of life and in reducing psychological distress and end-of-life despair. 415 advanced cancer patients, with Stage IV solid tumors and Distress Thermometer scores > 4, will be randomized to receive either IMCP, ISP, or EUC (138 patients randomized to each arm, anticipating an attrition rate of 35% would thus leave 90 patients per arm, or 270 patients, who complete the entire trial). In addition, we will examine variables that may moderate and mediate the effects of IMCP as well as the relative impact of IMCP on different aspects of spiritual well-being and meaning. Participants will be assessed with a battery of self-report measures at baseline/pre-intervention, mid-intervention, post-intervention, and at 2-month follow-up. This study will provide essential efficacy data on an innovative, 7-session, individual psychotherapy intervention for patients with advanced cancer, incorporating spiritual (meaning-centered) elements, which holds promise in the treatment of suffering at the end-of-life.